Recent reports suggest that the induction of ornithine decarboxylase (ODC; EC 4.1.1.17) activity may be an obligatory step in the tumor-promotion process. The involvement of adenosine cyclic 3',5'-phosphate (cAMP) and cAMP-dependent protein kinases in the mechanisms of activation of ODC has been demonstrated in a number of systems, suggesting that this may be a general phenomenon. A body of evidence is developing to show that there are at least two general types of cAMP-dependent protein kinases--Types I and II--that may fulfill different biological functions. We have observed that the topical application of a promoting dose of the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) results in the specific activation of Type II cAMP-dependent protein kinase. The objective of the proposed research is to further investigate the involvement of cAMP-dependent protein kinases in the induction of ODC activity by tumor-promoting agents. In the proposed research, we will examine the time course of the Type II kinase activation relative to the time course of ODC induction. We will compare the potency of a number of phorbol-type and non-phorbol-type tumor promoters to affect protein kinase activation and ODC induction. We will also compare the potency of a group of synthetic retinoids to inhibit both processes. Last, we will examine the association of the Type II kinase with the plasma membrane, the effect of TPA on this membrane-associated enzyme, and the activation of the kinase by TPA in isolated membranes.